The framework of this proposal is that the classic autism symptoms of social-cognitive deficits and restricted repetitive behaviors may both be characterized by dysregulated goal-directed responses to affective stimuli. Thus, we hypothesize that dysregulated neurobiological mechanisms mediating approach and withdrawal motivation may underlie these two seemingly disparate symptom domains. It has been argued that poorly modulated motivational responses are core features of other disorders, a conceptualization that has been fruitful because the neurobiological basis of goal-directed behaviors has been extensively studied in animal models, in human nonclinical contexts, and in human pathophysiological states. Additionally, because of established linkages between dysregulated motivational states and aberrant functioning of specific neurotransmitter systems, these lines of research have been successful in suggesting novel and effective treatment approaches in other disorders. We propose to leverage well-established psychophysiological measures of motivational states to assess the priming of neurobiologically-based defensive and appetitive systems in response to affective stimuli relevant to the autism behavioral phenotype. Specifically, we propose to measure affective modulation of psychophysiological responses to: (1) normative affective stimuli;(2) social stimuli, and (3) restricted interest stimuli in individuals with autism. Of prime relevance will be affective modulation of the startle eyeblink and postauricular reflex responses because, on theoretical grounds, they are ideally suited for assessing the response characteristics to social and restricted interest stimuli that are core features of autism. The project also represents an initial collaboration between two new members of NICHD Developmental Disabilities Research Centers (co-PI's Dr. Dichter at the University of North Carolina and Dr. Benning at Vanderbilt University) and brings together experts in the autism behavioral phenotype, psychophysiology, and child development to investigate a novel approach to characterizing the autism endophenotype. PUBLIC HEALTH RELEVANCE: This project seeks to better understand the pathophysiology of autism using painless and noninvasive psychophysiological measures. The information learned from this study would allow for future research that investigates whether these psychophysiological measures may have diagnostic utility and whether they may serve as biomarkers of treatment response.